Immunological heterogeneity in Ménière's disease: CD4+ T cell subset profiling reveals three distinct Immunophenotypes

IF 2.5 4区 医学 Q3 IMMUNOLOGY
Huaili Jiang , Yanxia Zhan , Menglong Zhao , Shujie Zhang , Lei Zhou , Kanglun Jiang , Yunfeng Cheng , Xinsheng Huang , Xiaofeng Xie
{"title":"Immunological heterogeneity in Ménière's disease: CD4+ T cell subset profiling reveals three distinct Immunophenotypes","authors":"Huaili Jiang ,&nbsp;Yanxia Zhan ,&nbsp;Menglong Zhao ,&nbsp;Shujie Zhang ,&nbsp;Lei Zhou ,&nbsp;Kanglun Jiang ,&nbsp;Yunfeng Cheng ,&nbsp;Xinsheng Huang ,&nbsp;Xiaofeng Xie","doi":"10.1016/j.jneuroim.2025.578743","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.</div></div><div><h3>Methods</h3><div>We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.</div></div><div><h3>Results</h3><div>Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (<em>p</em> &lt; 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, <em>p</em> = 0.007) and IFN-γ (HR = 0.26, <em>p</em> = 0.046) may represent biomarkers of disease activity.</div></div><div><h3>Conclusion</h3><div>MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578743"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165572825002243","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.

Methods

We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.

Results

Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (p < 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, p = 0.007) and IFN-γ (HR = 0.26, p = 0.046) may represent biomarkers of disease activity.

Conclusion

MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling
membroinitre病的免疫学异质性:CD4+ T细胞亚群分析揭示了三种不同的免疫表型
背景:mims是一种异质性疾病,发病机制尚不清楚。虽然涉及免疫失调,但CD4+ T细胞亚群的具体作用及其在MD中的临床相关性尚不清楚。方法采用流式细胞术对30例MD患者和27例健康对照者进行综合免疫分析,分析CD4+ T细胞6个亚群(Th1、Th2、Th17、Treg、TGF-β+、TNF-α+)和16种炎症介质及IgE的多重细胞因子。无监督的分层聚类识别出不同的免疫表型,cox回归分析确定了疾病活动的生物标志物。结果发现三种不同的免疫表型:自身炎症(35.7%,Th1/TNF-α +细胞升高),无活性(28.6%,平衡)和2型偏斜(35.7%,Treg/TGF-β +细胞升高)。MD患者Th1/Th2/Th17平衡明显改变,TGF-β +细胞升高(p < 0.001),血清IFN-γ、IL-1β和IL-17 a水平降低,CCL3/CCL4趋化因子升高。簇特异性免疫-临床相关性揭示了不同的病理生理模式。IL-2Rα (HR = 0.18, p = 0.007)和IFN-γ (HR = 0.26, p = 0.046)可能是疾病活动性的生物标志物。结论md具有明显的免疫异质性,具有三种不同的CD4+ T细胞定义表型。这些发现支持了个性化治疗方法的发展,并提示了疾病活动的潜在生物标志物,通过全面的免疫谱分析促进了我们对MD发病机制的理解
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of neuroimmunology
Journal of neuroimmunology 医学-免疫学
CiteScore
6.10
自引率
3.00%
发文量
154
审稿时长
37 days
期刊介绍: The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信